The first antibiotic was penicillin, which is now classified in the structural family of beta-lactam antibiotics. The beta-lactam antibiotics contain a beta-lactam ring, and generally act by inhibiting bacterial cell wall synthesis. Since the discovery of penicillin, hundreds of beta-lactam antibiotics have been isolated from natural sources or chemically synthesized. Beta-lactam antibiotics are still used widely to combat infections.
However, bacteria increasingly develop resistance to beta-lactam antibiotics. Resistance most often arises from beta-lactamase enzymes that degrade the antibiotics. To overcome the resistance, physicians sometimes administer compounds that inhibit beta-lactamase enzymes, known as beta-lactamase inhibitors, in conjunction with beta-lactam antibiotics. One commercially available combination of a beta-lactam antibiotic and a beta-lactamase inhibitor is Augmentin® (amoxicillin/clavulanate potassium), which contains the beta-lactam antibiotic amoxicillin and the beta-lactamase inhibitor clavulanic acid.
Augmentin® (amoxicillin/clavulanate potassium), and other beta-lactam antibiotic/beta-lactamase inhibitor combinations are typically administered orally or by systemic intravenous injection. Both these methods of administration require repeated administrations over a course of several days. This carries a risk of missed doses and patient non-compliance with finishing the course of therapy. Local administration is also sometimes desired to treat a localized infection. New formulations or methods for administering a combination of a beta-lactam antibiotic and a beta-lactamase inhibitor are currently needed. Preferably the new formulations would allow less frequent administration, would reduce the likelihood of patient non-compliance with finishing a course of therapy, or would allow sustained release. Preferably such new formulation might also allow local administration to a site of infection or a site at risk for infection, thereby reducing systemic exposure to the beta-lactam antibiotic, the beta-lactamase inhibitor, or both.